| Chronic dopamine replacement therapy in Parkinson's disease (PD) leads to deleterious motor sequelae known as L-DOPA-induced dysinesias (LID). The present study used the rat unilateral 6-hydroxydopamine model of PD to characterize and localize the efficacy of (+/-)propranolol, a beta-adrenergic receptor (betaAR) antagonist, in reducing LID when used as an adjunct to therapy with L-DOPA. We examined whether (+/-)propranolol was capable of reducing the development and expression of LID without impairing motor performance. PCR was used to examine the effects of (+/-)propranolol on striatal mRNA transcription. Subsequently, each enantiomer of (+/-)propranolol was examined separately in order to determine whether (+/-)propranolol reduces LID through betaAR blockade. Microinfusions were performed to investigate the effects of a localized striatal betaAR blockade on LID. Behaviorally, a dose range of (+/-)propranolol reduced LID without affecting motor activity. Overall, results suggest that (+/-)propranolol acts through betaAR antagonism in the striatum to reduce aberrant signaling associated with dyskinesia. |
